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Selective screening for lysosomal storage disorders in a large cohort of minorities of African descent shows high prevalence rates and novel variants
Population studies point to regional and ethnicity‐specific differences in genetic predisposition for some lysosomal storage disorders (LSDs). The aim of the study was to determine the prevalence of the three treatable forms of lysosomal storage disorders (Gaucher disease [GD], Pompe disease [PD], a...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100401/ https://www.ncbi.nlm.nih.gov/pubmed/33977031 http://dx.doi.org/10.1002/jmd2.12201 |
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author | Limgala, Renuka Pudi Furtak, Vyacheslav Ivanova, Margarita M. Changsila, Erk Wilks, Floyd Fidelia‐Lambert, Marie N. Goker‐Alpan, Ozlem Gondré‐Lewis, Marjorie C. |
author_facet | Limgala, Renuka Pudi Furtak, Vyacheslav Ivanova, Margarita M. Changsila, Erk Wilks, Floyd Fidelia‐Lambert, Marie N. Goker‐Alpan, Ozlem Gondré‐Lewis, Marjorie C. |
author_sort | Limgala, Renuka Pudi |
collection | PubMed |
description | Population studies point to regional and ethnicity‐specific differences in genetic predisposition for some lysosomal storage disorders (LSDs). The aim of the study was to determine the prevalence of the three treatable forms of lysosomal storage disorders (Gaucher disease [GD], Pompe disease [PD], and Fabry disease [FD]) in a cohort of mostly urban‐dwelling individuals of African ancestry, a previously unknown genetic landscape for LSDs. Large‐scale selective multistep biochemical and genetic screening was performed in patients seeking healthcare for various health concerns. Fluorimetric enzyme assays for GD, PD, and FD were performed on dried blood spots. Targeted gene sequencing was performed on samples that showed significantly lower enzyme activities (<10% of control mean) after two tiers of enzymatic screening. A total of 5287 unique samples representing a cross section of patients who visited Howard University Hospital and College of Medicine from 2015 to 2017 were included in the study. Study samples were obtained from a population where ~90% reported as African‐American, ~5% Hispanic, and <5% Caucasian or other. Regarding GD, three subjects had either homozygous or heterozygous mutations in the GBA gene. As to PD, eight subjects were either homozygous or compound heterozygous for GAA mutations, including three novel mutations: (a) c.472 A > G; p.T158A, (b) c.503G > T; p.R168L, (c) c.1985del. Regarding FD, two subjects had pathogenic GLA mutations, and four had single nucleotide polymorphisms in the 5'UTR, previously implicated in modulating gene expression. The findings highlight a higher incidence of abnormal enzyme levels and pathogenic mutations in the target population reflecting ancestry‐based specific genotype and phenotype variations. |
format | Online Article Text |
id | pubmed-8100401 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81004012021-05-10 Selective screening for lysosomal storage disorders in a large cohort of minorities of African descent shows high prevalence rates and novel variants Limgala, Renuka Pudi Furtak, Vyacheslav Ivanova, Margarita M. Changsila, Erk Wilks, Floyd Fidelia‐Lambert, Marie N. Goker‐Alpan, Ozlem Gondré‐Lewis, Marjorie C. JIMD Rep Research Reports Population studies point to regional and ethnicity‐specific differences in genetic predisposition for some lysosomal storage disorders (LSDs). The aim of the study was to determine the prevalence of the three treatable forms of lysosomal storage disorders (Gaucher disease [GD], Pompe disease [PD], and Fabry disease [FD]) in a cohort of mostly urban‐dwelling individuals of African ancestry, a previously unknown genetic landscape for LSDs. Large‐scale selective multistep biochemical and genetic screening was performed in patients seeking healthcare for various health concerns. Fluorimetric enzyme assays for GD, PD, and FD were performed on dried blood spots. Targeted gene sequencing was performed on samples that showed significantly lower enzyme activities (<10% of control mean) after two tiers of enzymatic screening. A total of 5287 unique samples representing a cross section of patients who visited Howard University Hospital and College of Medicine from 2015 to 2017 were included in the study. Study samples were obtained from a population where ~90% reported as African‐American, ~5% Hispanic, and <5% Caucasian or other. Regarding GD, three subjects had either homozygous or heterozygous mutations in the GBA gene. As to PD, eight subjects were either homozygous or compound heterozygous for GAA mutations, including three novel mutations: (a) c.472 A > G; p.T158A, (b) c.503G > T; p.R168L, (c) c.1985del. Regarding FD, two subjects had pathogenic GLA mutations, and four had single nucleotide polymorphisms in the 5'UTR, previously implicated in modulating gene expression. The findings highlight a higher incidence of abnormal enzyme levels and pathogenic mutations in the target population reflecting ancestry‐based specific genotype and phenotype variations. John Wiley & Sons, Inc. 2021-01-27 /pmc/articles/PMC8100401/ /pubmed/33977031 http://dx.doi.org/10.1002/jmd2.12201 Text en © 2021 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Reports Limgala, Renuka Pudi Furtak, Vyacheslav Ivanova, Margarita M. Changsila, Erk Wilks, Floyd Fidelia‐Lambert, Marie N. Goker‐Alpan, Ozlem Gondré‐Lewis, Marjorie C. Selective screening for lysosomal storage disorders in a large cohort of minorities of African descent shows high prevalence rates and novel variants |
title | Selective screening for lysosomal storage disorders in a large cohort of minorities of African descent shows high prevalence rates and novel variants |
title_full | Selective screening for lysosomal storage disorders in a large cohort of minorities of African descent shows high prevalence rates and novel variants |
title_fullStr | Selective screening for lysosomal storage disorders in a large cohort of minorities of African descent shows high prevalence rates and novel variants |
title_full_unstemmed | Selective screening for lysosomal storage disorders in a large cohort of minorities of African descent shows high prevalence rates and novel variants |
title_short | Selective screening for lysosomal storage disorders in a large cohort of minorities of African descent shows high prevalence rates and novel variants |
title_sort | selective screening for lysosomal storage disorders in a large cohort of minorities of african descent shows high prevalence rates and novel variants |
topic | Research Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100401/ https://www.ncbi.nlm.nih.gov/pubmed/33977031 http://dx.doi.org/10.1002/jmd2.12201 |
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